scholarly journals The Repurposing of the Antimalaria Drug, Primaquine, as a Photosensitizer to Inactivate Cryptococcal Cells

Photochem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 275-286
Author(s):  
Uju L. Madu ◽  
Adepemi O. Ogundeji ◽  
Olufemi S. Folorunso ◽  
Jacobus Albertyn ◽  
Carolina H. Pohl ◽  
...  

Cryptococcal cells can manifest skin infections in immunocompromised persons. While it may be easy to diagnose cryptococcal infection, treatment often fails due to the ineffectiveness of current antifungal agents. To this end, the present study explored the repurposing of primaquine (PQ), as a photosensitizer. PDT was carried out using a germicidal ultraviolet (UV) lamp, which has a radiation output of approximately 625 µW/cm2 at a distance of 20 cm. When compared to the non-treated cells, the metabolic activity of cryptococcal cells was significantly (p < 0.05) limited. The photolytic products of PQ were observed to alter the ultrastructure of treated cells. The latter was not incidental, as the same cells were also documented to lose their selective permeability. Importantly, PDT also improved the efficiency of macrophages to kill internalized cryptococcal cells (p ≤ 0.05) when compared to non-treated macrophages. Equally importantly, PDT was not detrimental to macrophages, as their metabolic activity was not significantly (p > 0.05) limited, even when exposed to 20× the MIC (determined for cryptococcal cells) and an exposure time that was 4× longer. Taken together, the results suggest PQ has the potential to control the growth of cryptococcal cells and limit their survival inside the macrophage.

Author(s):  
Sung Hong Kim ◽  
Young Gyun Choi ◽  
Dooil Kim

Fouling on the quartz sleeve reduces the transmittance of UV light through the sleeve into the water in submerged UV disinfection system. The concept of a non-contact type of UV disinfection system was introduced in this study. UV lamps and their quartz sleeves hang over the water surface and there is no interface between the sleeve and water. Indeed, there is no fouling. Based on optical laws and UV distribution model, a detailed mathematical model for a non-contact type UV disinfection system was developed and simulated in this study. UV light passes through 4 media of air-quartz-air and water in case of non-contact type irradiation system. By the simulation of the mathematical model of the system, it is known that the non-contact type of UV system requires 2.5 times more powerful UV lamp or a lamp with longer exposure time than that of the submerged type of UV system. In a non-contact type of UV system, high-reflective ceiling material can increase the UV intensity of the water layer as much as 28 percent more than the case of non-reflective ceiling material. The non-contact type UV irradiation system requires more powerful lamp or one that have longer exposure time. Nevertheless, considering the fouling attenuation and maintenance problem associated with the fouling, non-contact type of UV disinfection system deserves to be practically considered, especially in a small to middle scale water or wastewater treatment plant.


2012 ◽  
Vol 23 (6) ◽  
pp. 716-722 ◽  
Author(s):  
Wander José da Silva ◽  
Letícia Machado Gonçalves ◽  
Jayampath Seneviratne ◽  
Nipuna Parahitiyawa ◽  
Lakshman Perera Samaranayake ◽  
...  

This study aimed to evaluate the effects of fluconazole or nystatin exposure on developed Candida albicans biofilms regarding their exopolysaccharide matrix. The minimal inhibitory concentration (MIC) against fluconazole or nystatin was determined for C. albicans reference strain (ATCC 90028). Poly(methlymethacrylate) resin (PMMA) specimens were fabricated according to the manufacturer's instructions and had their surface roughness measured. Biofilms were developed on specimens surfaces for 48 h and after that were exposed during 24 h to fluconazole or nystatin prepared in a medium at MIC, 10 x MIC or 100 x MIC. Metabolic activity was evaluated using an XTT assay. Production of soluble and insoluble exopolysaccharide and intracellular polysaccharides was evaluated by the phenol-sulfuric method. Confocal laser scanning microscope was used to evaluate biofilm architecture and percentage of dead/live cells. Data were analyzed statistically by ANOVA and Tukey's test at 5% significance level. The presence of fluconazole or nystatin at concentrations higher than MIC results in a great reduction of metabolic activity (p<0.001). At MIC or 10 x MIC, fluconazole showed high amounts of intracellular polysaccharides (p<0.05), but did not affect the exopolysaccharide matrix (p>0.05). The exposure to nystatin also did not alter the exopolysaccharide matrix at all the tested concentrations (p>0.05). Biofilm architecture was not affected by either of the antifungal agents (p>0.05). Nystatin promoted higher proportion of dead cells (p<0.05). It may be concluded that fluconazole and nystatin above the MIC concentration reduced the metabolic activity of C. albicans biofilms; however, they were not able to alter the exopolysaccharide matrix and biofilm architecture.


2016 ◽  
Vol 1133 ◽  
pp. 399-403
Author(s):  
Nurul Najua Zulkepely ◽  
Siti Nurasiah Mat Nawi ◽  
Norfadira Wahib ◽  
Yusoff Mohd Amin ◽  
Roslan Md Nor ◽  
...  

In this paper we report, the characteristics of PTTL after irradiation with 60Co gamma rays as a function UV light exposure wavelength, gamma irradiation dose, and UV light exposure time were determined for Ge-doped SiO2 optical fibers. The efficiency of dose reassessment for this fiber was compared to standard thermoluminescence detector, TLD100. Experiments show that the method works well with the UV lamp of 254 nm within region of doses between 3 to 50 Gy, but could be applied for higher and lower doses as well. The effect of exposure time of UV radiation on the PTTL signal was studied from 5 to 120 minutes to determine the highest sensitivity and the limit of the dose. The efficiency of dose reassessment with 10 Gy of gamma irradiation expose to UV light for 15 minutes relative to PTTL values of about 27.0% and 2.3% for Ge-doped SiO2 optical fiber and TLD100.


2012 ◽  
Vol 472-475 ◽  
pp. 1361-1365
Author(s):  
Do Yeon Jung ◽  
Abdallah Abdel Hay ◽  
Jao Kyoo Lim

Abstract. In present study, the effect of irradiation along with applied load and three periods on the ultraviolet (UV) aging of the polycarbonate polymer was investigated by observing the changes in the mechanical properties. Dog bone specimens of polycarbonate were subjected to different test conditions namely in the amount of applied load and the variation in exposure time to the UV lamp. The results showed that, with a constant applied load of 1kN, increase in the exposure time in UV radiation caused the mechanical properties to relatively increase at first and decrease gradually afterwards. However, for constant exposure time, the tensile strength showed much decrease with increase in applied load. For the test conducted at higher applied load of 3kN, the mechanical properties of material relatively improves in a drastic manner for the higher exposure time. It was inferred that the increase in applied load has a crucial role in the UV aging of polycarbonate for the given exposure time. Moreover, the morphology of the fracture area under different test conditions was observed by Scanning Electron Microscope (SEM).


1994 ◽  
Vol 7 (4) ◽  
pp. 479-504 ◽  
Author(s):  
P E Nelson ◽  
M C Dignani ◽  
E J Anaissie

There are several taxonomic systems available for identifying Fusarium species. The philosophy used in each taxonomic system is discussed as well as problems encountered in working with Fusarium species in culture. Fusarium species are toxigenic, and the mycotoxins produced by these organisms are often associated with animal and human diseases. The implications for the association of the carcinogens, fumonisins, produced by Fusarium moniliforme and other Fusarium species with human diseases are discussed. Foreign-body-associated fusarial infection such as keratitis in contact lens wearers, onychomycosis, skin infections, and disseminated multiorgan infections are discussed. Disseminated fusarial hyalohyphomycosis has emerged as a significant, usually fatal infection in the immunocompromised host. Successful outcome is determined by the degree of immunosuppression, the extent of the infection, and the presence of a removable focus such as an indwelling central venous catheter. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy, probably with one of the newer antifungal agents. Perhaps the use of such agents or the use of colony-stimulating factors may improve the outcome of this devastating infection. However, until new approaches for treatment develop, effective preventive measures are urgently needed.


Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Fengyuan Wang ◽  
Xiaoxuan Zhang ◽  
Guopu Chen ◽  
Yuanjin Zhao

Fungal infections are everlasting health challenges all over the world, bringing about great financial and medical burdens. Here, inspired by the natural competition law of beneficial bacteria against other microbes, we present novel living microneedles (LMNs) with functionalized bacteria encapsulation for efficient fungal infection treatment. The chosen beneficial bacterial components, Bacillus subtilis (B. subtilis), which are naturally found on the human skin and widely used for food processing, can get nutrients from the skin and escape from the immune system with the help of microneedles. Besides, the encapsulated B. subtilis can continuously produce and secrete various potential antifungal agents which can directly bind to fungal cell surface-associated proteins and destruct the cell membranes, thus avoiding drug resistance. After immobilization in the LMNs, the bacteria can stay within the LMNs without invasion and the encapsulated bacteria together with microneedles can be removed after application. Thus, the side effects, especially the risk for subsequent bacterial infections, are controlled to a minimum to ensure security. In addition, strong penetrability of the microneedles enhances penetration of antifungal agents, and their heights can be adjusted according to the infected depth to acquire better therapeutic effects. These features make the LMNs potentially valuable for clinical applications.


Author(s):  
F. A. Heckman ◽  
E. Redman ◽  
J.E. Connolly

In our initial publication on this subject1) we reported results demonstrating that contrast is the most important factor in producing the high image quality required for reliable image analysis. We also listed the factors which enhance contrast in order of the experimentally determined magnitude of their effect. The two most powerful factors affecting image contrast attainable with sheet film are beam intensity and KV. At that time we had only qualitative evidence for the ranking of enhancing factors. Later we carried out the densitometric measurements which led to the results outlined below.Meaningful evaluations of the cause-effect relationships among the considerable number of variables in preparing EM negatives depend on doing things in a systematic way, varying only one parameter at a time. Unless otherwise noted, we adhered to the following procedure evolved during our comprehensive study:Philips EM-300; 30μ objective aperature; magnification 7000- 12000X, exposure time 1 second, anti-contamination device operating.


Author(s):  
W. Kuenzig ◽  
M. Boublik ◽  
J.J. Kamm ◽  
J.J. Burns

Unlike a variety of other animal species, such as the rabbit, mouse or rat, the guinea pig has a relatively long gestation period and is a more fully developed animal at birth. Kuenzig et al. reported that drug metabolic activity which increases very slowly during fetal life, increases rapidly after birth. Hepatocytes of a 3-day old neonate metabolize drugs and reduce cytochrome P-450 at a rate comparable to that observed in the adult animal. Moreover the administration of drugs like phenobarbital to pregnant guinea pigs increases the microsomal mixed function oxidase activity already in the fetus.Drug metabolic activity is, generally, localized within the smooth endoplasmic reticulum (SER) of the hepatocyte.


Author(s):  
C. W. Kischer

The morphology of the fibroblasts changes markedly as the healing period from burn wounds progresses, through development of the hypertrophic scar, to resolution of the scar by a self-limiting process of maturation or therapeutic resolution. In addition, hypertrophic scars contain an increased cell proliferation largely made up of fibroblasts. This tremendous population of fibroblasts seems congruous with the abundance of collagen and ground substance. The fine structure of these cells should reflect some aspects of the metabolic activity necessary for production of the scar, and might presage the stage of maturation.A comparison of the fine structure of the fibroblasts from normal skin, different scar types, and granulation tissue has been made by transmission (TEM) and scanning electron microscopy (SEM).


Author(s):  
G. M. Kozubov

The ultrastructure of reproductive organs of pine, spruce, larch and ginkgo was investigated. It was found that the male reproductive organs possess similar organization. The most considerable change in the ultrastructure of the microsporocytes occur in meiosis. Sporoderm is being laid at the late tetrad stage. The cells of the male gameto-phyte are distinguished according to the metabolic activity of the or- ganells. They are most weakly developed in the spermiogenic cell. Ta-petum of the gymnosperms is of the periplasmodic - secretorial type. The Ubisch bodies which possess similar structure in the types investigated but are specific in details in different species are produced in tapetum.Parietal and subepidermal layers are distinguished for their high metabolic activity and are capable of the autonomous photosynthesis. Female reproductive organs differ more greatly in their struture and have the most complicated structure in primitive groups. On the first stages of their formation the inner cells of nucellus are transformed into the nucellar tapetum in which the structures similar to the Ubisch bodies taking part in the formation of the sporoderm of female gametophyte have been found.


Sign in / Sign up

Export Citation Format

Share Document